JPS62153281A - 6-(1,4-dimethoxy-5,8-dioxonaphthalen-2-yl)-3,4,5,6-tetr-ahydro-2h-pyran derivative - Google Patents

Abstract

NEW MATERIAL:A compound shown by formula I (R<1> is OH-protecting group). EXAMPLE:(3R,4R,5R,6R)-6-(1,4-Dimethoxy-5,8-dioxonaphthalen-2-yl)-4-dim ethyla mino-2,3,5-trimetkoxymethyloxy-6-methyl-3,4,5,6--tetrahydro-2H-pyan. USE:A carcinostatic agent. PREPARATION:Lithium slat of 1,4,5,8-tetramethoxynaphtahlene is added to a compound shown by formula II to give a compound shown by formula III. Then, its t-butyldimethylsilyl group is removed and the reaction product is oxidized to give a compound shown by formula IV. This compound is then reduced, and a protecting group is introduced to hydroxyl group at the 2-position of the prepared compound shown by formula V and the reaction product is reduced to give a compound shown by formula VI. Further this compound is oxidized to give a compound shown by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION Toxi-5,8-dioxonaphthalen-2-yl)-new leaves! 3.4,5.6-Titrahydro 2H-bilane derivatives.

[Conventional technology]

There is a strong demand from society for the development of excellent anticancer drugs.
Various anticancer drugs occupy an important position in medicine.

Generally, the anticancer activity of a compound is largely dependent on its chemical structure, and therefore, it is extremely likely that a compound that can be put to practical use as an excellent anticancer agent will be found among those having a structure different from known ones.

[Problems to be solved by the present invention]

The object of the present invention is to develop novel 6-(1,4-
dimethoxy-5,8-dioxonaphthalen-2-yl)
-3,4,5,6-tetra derivative -2H-bilane derivative.

[Means for solving problems]

The present invention provides novel 6-(1,4-dimethoxy-5,8-dioxonaphthalen-2-yl)-3, 4,5゜6-tetrahydro-
It is a 2H-bilane derivative.

6-(1,4-dimethoxy-5,8-dioxonaphthalene-2-inole) represented by the general formula (I) 3.4
, 5,6-titrahydro-2H-bilane derivatives can be produced according to the following reaction formula.

(JMe OMe lJMe L)Nle (In the formula, 几1 is a hydroxyl group.) [First step] This step is performed by adding the hexan-2-one derivative of the formula (11) to the hexan-2-one derivative of the formula (11). 1, 4, 5°8- expressed as (1)
A 2-hexanol transparent conductor represented by the above formula (1) is produced by adding a lithium salt of tetramethoxynaphthalene.

6-t-Butyldimethylsilyloxy-4-(N-methoxycarbonyl-N-methyl)amino-3,5-dimethoxymethyloxy-hexane-2- which is the raw material for this step
) is a compound that can be synthesized by known methods (
M., Kawasakj, et al.

Tetrahedron Lett, 26, 26
93 (1985)).

The addition reaction in this step is preferably carried out in a solvent, and for example, ether solvents such as tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, and dioxane can be used.

The reaction proceeds smoothly at -78°C to 50°C.

[Second step] This step removes the t-butyldimethylsilyl group of the 2-hexyl alcohol conductor represented by the formula W) obtained in the first step to obtain 1°5-hexane represented by the above This method produces diol derivatives.

In removing the protecting group in this step, for example, tetrabutylammonium fluoride, hydrofluoric acid, acetic acid, etc. can be used as a desilylating agent.

This step is preferably carried out in a solvent, such as diethyl ether, tetrahydrofuran, 1.2-
Ether solvents such as dimethoxyethane and dioxane, and halogenated hydrocarbon solvents such as chloroform and dichloromethane can be used.

The reaction proceeds smoothly at a temperature of O″c-ioooC.

[Third Step] This step oxidizes the isomer of 1,5-hexanediol represented by the formula (7) obtained in the second step to obtain 6-(1,4, A 5,8-tetramethoxynaphthalen-2-yl)-3°4.5.6-tetrahydro-2-pyranone derivative is produced.

In the oxidation in this step, for example, dimethyl sulfoxide/oxalyl chloride/triethylamine mixed oxidizing agent, dimethyl sulfoxide/trifluoroacetic anhydride/triethylamine mixed oxidizing agent, pyridinium chlorochromate, etc. can be used.

This step is preferably carried out in a solvent, and for example, halogenated hydrocarbon solvents such as chloroform, dichloroethane, and dichloroethane can be used.

The reaction temperature is -60°C to 50°C, and the process proceeds smoothly [4th step] This step is carried out using 6-(1,4,5,8-tetramethoxy expressed by VD) obtained in the third step. 6-(1,
4,5,8-tetramethoxynaphthalen-2-yl)-
A 3,4,5,6-tetrahydro 2H-bilane derivative is produced.

In the reduction in this step, for example, diisobutylaluminum hydride, hydrogenated tri-1-butoxyaluminum lithium, etc. can be used as a reducing agent.

This step is preferably carried out in a solvent, such as diethyl ether, tetrahydrofuran, 1.2-
Ether solvents such as dimethoxyethane and hydrocarbon solvents such as toluene and hexane can be used.

The reaction proceeds smoothly at a temperature of -78°C-o'c.

[Fifth Step] This step converts 6-(1,4,5,8-tetramethoxynaphthalene-
2-yl)-3,4,5,6-tetrahydro-2ti-
Bilane derivative 6-(1,4,5,8-tetramethoxynaphthalen-2-yl)-3,4,5,6- by introducing a hydroxyl group into the hydroxyl group at the 2-position θc and represented by the above general formula -
A tetrahydro-2H-bilane derivative is produced.

As the hydroxyl protecting group used in this step, alkyl groups such as methyl group, t-butyl group, allyl group, 2,2,2-trichloroethyl group, benzyl group, p-methoxybenzyl group, and arylmethyl group, trimethylsilyl group,
triethylsilyl group, isopropyldimethylsilyl group,
Trialkylsilyl groups such as t-butyldimethylsilyl group and t-butyldiphenylsilyl group, methoxymethyl group,
2-methoxyethoxymethyl group, benzyloxymethyl group, 2-trimethylsilylethoxymethyl group, 2.2.
Examples include alkoxymethyl groups such as 2-1-lichloroethoxymethyl, alkyl and arylthiomethyl groups such as methylthiomethyl, and phenylthiomethyl.

These protecting groups can be prepared by methods known to those skilled in the art (C, B, 1k
ese, “Protective Groups i
n Organic Chemistry, ed.
by J.

F., W., Mcαnie, Plenum Press, L.
ondon and New York, t973. pp
9s-t44; T, W, Greene.

”Protective Groups in Org
anic chemistry”.

John Wiley & 5ons, New Year
k, 1981, pPIO-86; Takeshi Oishi, Yugo,
715 (1978), ).

When introducing an alkoxymethyl group as a protecting group for the hydroxyl group of the above general formula &I, by reacting a halogenated alkoxymethyl with the presence of diisopropylethylamine, a compound represented by ==---6 above general formula ~υ 6-(1,4,5,8-tetramethoxynaphthalene-2
-3°4.5.6-tetrahydro-2H-bilane conductor can be prepared. Examples of the alkoxymethyl halide used in the dialkoxymethylation include methoxymethyl chloride, methoxymethyl bromide, and 2-methoxyethoxymethychloride. This step can also be carried out without solvent, but
For example, diethyl ether, tetrahydrofuran, 1.
It can also be carried out by adding an ether solvent such as 2-dimethoxyethane or dioxane. Reaction temperature is room temperature ~ 8
Proceeds smoothly at 0°C.

[Sixth step] This step is performed to obtain the 6-(1,4,5,8-tetramethoxynaphthalen-2-yl)-3,4,5,6 represented by the general formula - obtained in the fifth step. -tetrahydro-2H-
6 which reduces the Bilan visiting conductor and is given by the general formula (2) above.
-(1,4,5,8-tetramethoxynaphthalene-2-
yl)-3,4°5,6-tetrahydro-2H-bilane derivative.

In the reduction in this step, for example, lithium aluminum hydride, lithium borohydride, etc. can be used as a reducing agent.

This step is preferably carried out in a solvent, and ether solvents such as diethyl ether, tetrahydrofuran 1,2-dimethoxyethane, and dioxane can be used.

The reaction proceeds smoothly at a temperature of 0°C to 80°C.

[Seventh Step] This step is performed to obtain 6-(1,4,5,8-tetramethoxynaphthalen-2-yl)-3,4,5, 6-tetrahydro-2H-
By oxidizing Bilane conductor, 6-(1,4-dimethoxy-5,8-dioxonaphthalen-2-yl)-3,4,5,6-tetrahydro-2H represented by the above general formula (1)
- for producing biran derivatives. Cerium ammonium nitrate can be selected as the oxidizing agent.

This step is preferably carried out in a solvent, and for example, an alcoholic solvent such as methanol, ethanol, propatool, etc., or a polar solvent such as acetonitrile, dimethylformamide, dimethylacetamide, etc. can be used.

The reaction proceeds smoothly at a temperature of -50°C to 50°C.

6-(1,4-dimethoxy-5,8-dioxonaphthalen-2-yl)-3,4,5,6-tetrahydro-2H represented by the general formula (1) obtained as above.
- The usefulness of the bilan derivative as an anticancer agent was confirmed by conducting a malignant tumor cell growth inhibition test.

The test was conducted using mouse lymphocytic leukemia cells (93 gg) according to a conventional method, and the inhibition rate was determined.

The present invention will be described in detail below with reference to Reference Examples, Examples, and Test Examples.

112\gom- Reference example 1 1.4,5.8-tetramethoxynaphthalene (m, p,
Dissolve 1.74 g (7.0 mmol) of n-butyl lithium in hexane solution (1,2
7 molar concentration) at 5.5°C m1 (7.0 mmol) was added,
Stirring was further continued at that temperature for 20 minutes. (-)-(3
R,4S,53)-5-t-butylphthylsilyloxy-3,5-dimethoxymethyloxy-4-(N-methoxycarbonyl-N-methylgemiμξ2-hexanone (T
etra,hedron Lett,,26°269
3 (1985)) 2.13g (
4,9 mmol l) of anhydrous tetrahydrofuran solution 15
m1 was added dropwise over 30 seconds at 0°C. Stirring was further continued at that temperature for 3 minutes. Subsequently, 100 ml of a saturated ammonium chloride aqueous solution was added to stop the reaction. After adding 200 ml of toluene and stirring, the organic layer was separated, washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was passed through a silica gel column (n
-Hexane/ethyl acetate (3) followed by chloroform/ethyl acetate (-)-(2R,3R).

4S, 53) -6-t-butyldimethylsilyloxy-
3,5-dimethoxymethyloxy-4-(N-methoxycarbonyl-N-methyl)amino-2-(1,4,5,
1.90 g (57% yield) of 8-tetramethoxynaphthalen-2-yl)-2-hexanol was obtained as a pale yellow caramel.

[α) ”-35,5 (cm1.oo chloroform) Mass spectrum m/e685 (M”).

NMR (CDCIs) δ (ppm): 0.03゜0
．． 05 (6H, 2s, Si (CH) dew).

0.86, 0.90 (9H, 2g.

S i C(CHs) ri, 1.76 (3H,
s.

3H+), 3.02 (3H,s, NCHs).

3.10.3.29, 3.33.3.37.3.55°3.64, 3.7G, 3.81, 3.84.3.86°ts 3.89 (2180CHs), 2. 9-5.0
(10H, m, OH, 0CHtX 3゜Hs, Ha, H
s), 6.84 (2)(, s.

ArH), 7.00 (IH, s, ArH).

IR (naa t): 3'450 (OH).

1690 (Co), 1600 (Ar) cm-'.

Elemental analysis value: CxxH□No, Calculated value as S1: C; 57.79. H, 8,0B.

N: 2.04%.

Analysis value: c; 57.76, H; 7.93°N;
1.99%.

Reference Example 2 (-) -(2R,3R,43,53) -6-t-butyldimethylsilyloxy-3,5-dimethoxymethyloxy-4-(N-methoxycarbonyl-N-methyl)
Amino-2-(l,4.5.8=tetramethoxynaphthalen-2-yl)-2-hexanol 1.50 g (
2,19 mmo 1) in anhydrous tetrahydrofuran 50
Dissolve the tetrabutylammonilla in 5.0 ml of diluted tetrahydrofuran solution (1 molar concentration) at 25°C with stirring.
5.0 mmol) was added thereto, and stirring was continued at that temperature for 1 hour. After distilling off the solvent, the residue was passed through a silica gel column (ethyl acetate)-)-(23°3S,4R,5R)-3
-(N-methoxycarbonyl-N-methyl)amino-2
,4-dimethoxymethyloxy-5-(1,4,5,8
-Tetramethoxynaphthalen-2-yl)-1,5-hexane 1 yen and 22 g (98% yield) of roux were obtained as colorless caramel.

[α) ”-31,4 = (c-1,25 chloroform, m) mass spectrum m/a 571 (M”).

NMR (CDCI,) δ (ppm): 1.73 (
3H,s, 3Hb), 2.96 (3H,s.

NCHs), 3.2 4.1 (28H, m.

7 CHx, 2 H+, Hz, Hko, H4゜20H),
4.4-5.0 (4H, m.

OCHgOX2), 6.81 (2H, s.

ArH), T, Q5.7.22 (11L 2s, A
rH).

IR (neat): 3450 (OH).

1680 (Co), 1600 (Ar) cm-
'.

Reference example 3 Oxalyl chloride 0.38 g (3.0 mmo 1
) was dissolved in 25 ml of anhydrous dichloromethane, and while stirring at -60°C, dimethyl sulfoxide o, s (
5 ml of anhydrous dichloromethane solution of 7.0 mmol was added and stirred at that temperature for 2 minutes. (-)-(23,33
,4R,5R)-3-(N-methoxycarbonyl-N-
methyl)amino-2,4-simethoxymethyloxy-5
- (1,4,5,8-tetramethoxynaphthalene-2
-yl)-1° Anhydrous dichloromethane solution (5 ml) was added and stirred at -60°C for 20 minutes. At this temperature, 1.52 g (15.0 mmol +) of triethylamine was added dropwise, and the reaction temperature was increased over 20 minutes. The temperature was raised to 0°C. 100ml of saturated ammonium chloride aqueous solution and 10ml of ethyl acetate
The reaction was stopped by adding 0ml. The organic layer was separated, suspended, washed with saturated brine (20 ml x 2), dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane-2) to obtain 0.82 g (91% yield) of (3S
, 4R, 5R, 6R)-4-(N-methoxycarbonyl-N-methyl)amino-3,5-dimethoxymethyloxy-6- was obtained.

Mass spectrum: m/5567 (M”).

NMR(CDCls)δ(ppm): 2.0
4 (3H, s, 6 CH3), 2.97
(3H.

s, NCHs), 3.20, 3.36 (6H.

2s, 0CHsX2), 3.66.3.70°3.8
6, 3.90, 3.92 (15H, 5s.

Ar0CH3X4. CO*CHi), 4.56(2H,
dd, J = 7Hz, 8Hz.

OCH*O), 4.92 (2)1. dd, J-36H
z, 7 Hz, OCH*O), 6.84(
2H,s, ArH), 7.00 (LH.

s, ArH).

IR (neat): 174G (Co).

1695 (Co), 1600 (Ar).

1025 (-0) cs-'.

Reference Example 4 (33,4R,5R,6R,)-4-(N-methoxycarbonyl-N-methyl)amino-3,5-lanone 435
g (0.77 mmol 1) was dissolved in 30 ml of anhydrous toluene, and while stirring at -78°C, a hexane solution (1.0 molar concentration) of diisobutylaluminum hydride was added.
92 ml (0.92 mmol 1) was added dropwise and stirred at this temperature for 20 minutes. Add 5 ml of methanol Q to stop the reaction, and add 100 ml of saturated ammonium chloride aqueous solution.
ml was added and extracted with ethyl acetate (30ml x 2).

The organic layers were combined, washed with saturated brine (20 ml x 2), dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure.

Dissolve the residue in 30 ml of methanol and add 2 ml of anhydrous potassium carbonate.
．． After adding Og and heating under reflux for 30 minutes, the reaction solution was filtered, and the filtrate was concentrated under reduced pressure. This product was purified by silica gel column chromatography (ethyl acetate/hexane-2 Ide)-(3S,4R,5R,6R)-2-
Hydroxy-4-(N-methoxycarbonyl-N-methyl)amino-3,5-dimethoxymethyloxy-6-methyl-6-(1,4,5,8-tetramethoxynaphthalen-2-yl)-3, 4,5,6-tetrahydro-2H
-Pyran 354 (82% yield) was obtained as a pale yellow caramel.

[α] 2°+12.1° (C-1,05 chloroform) MW spectrum m/e569 (M”).

NMR (CDCIs) δ (ppm): 1.83°1.91 (3H, 2s, 6-CHs).

2.96. 2.99 (3H, 2s, NCH Ri.

3.28 (3H, s, 0CHs), 3.37 (
3M, s, 0CHs), 3.44.3 (19H, m,
OC [i3X 4. COgCHs.

OH, HI H,, Hs), 4.4-4.9 (5
H, m, 0CH3X2. Ht), 6.80(2H,s,
ArH), 7.72 (IH,s.

Arc).

IR (neat): 3450 (OH)
.

1690 (Co), 1600 (Ar).

1070, 1030 (0) am-'.

(+)-(33,4R,5R,6R)-2-hydroxy-4-(N-methoxycarbonyl-N-methyl)amino-3,5-dimethoxymethyloxy-6-methyl-6-
(1,4,5,8-tetramethoxynaphthalen-2-yl)-3,4,5゜6-tetrahydro-2H-pyran 3
Dissolve 0.62 mmol of diisopropylethylamine in 5.0 ml of anhydrous tetrahydrofuran.
After adding 44 g (34 mmol 1) and 3.181 (39 mmol) of methyl ether, the mixture was heated under reflux for 3 hours. Subsequently, 2 m of triethylamine was added under water-cooling and stirring.
1 and 3 ml of methanol were added, and the mixture was left at this temperature for 15 minutes, and then 80 ml of ethyl acetate was added. The organic layer was washed successively with cold 3N HCl water, saturated aqueous sodium bicarbonate, and saturated brine, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane-2) to give (-)-(3S, 4R, 5
R.

6R)-4(N-methoxycarbonyl-N-methyl)amino-2,3,5-)rimethoxymethyloxy-6-methyl-6-(1,4,5,8-tetramethoxynaphthalen-2-yl' )3,4.5゜6-tetrahydro2
H-pyran 343 (91% yield) was obtained as colorless crystals.

m, p, 115-116°C.

[α) "-16,2° (C-1,10 chloroform) mass spectrum m/e 613 (M'").

NMR (CDCIs) δ (ppm) 71.82 (3
H, s, G CHs), 2.96°3.00 (3
H, 2s, NCHs), 3.23° 3.2B, 3.40
(9H, 3s, 0CI (ri x 3), 3.5 4
．． 3 (17tt, fn.

0CHsX5. Hs, Hs), 4.3 5.3 (2
H,s, ArH), 7.74 (LH,s.

ArH).

IR (KBr): 1700 (Co), 16
00(Ar), 1020(-0-)C
11-'.

Elemental analysis value: C□Calculated value as H45NOts: C
; 56.76, H; 7.06°Ni2.28%.

Analysis value: Ci 56.63. Hi 7.1? .

Ni2.21%.

Reference example 6! (-)-(33,4R,5R,6R)-4-(N-methoxycarbonyl-N-methyl)amino-2,3,5-)
dimethoxymethyloxy-6-methyl-6-(1,4,
5,8-tetramethoxynaphthalen-2-yl)-3,
4,5,6-tetra was dissolved in 40 ml of anhydrous ether, aluminum hydride was heated under reflux for 1 hour, and then 1 ml of methanol was added to stop the reaction. 100 ml of ethyl acetate was added, and the organic layer was washed with saturated brine (20 ml x 3), dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.

The residue was purified by silica gel column chromatography (ethyl acetate/hexane-2).
R,6R)-4-dimethylamino-2,3,5-1-dimethoxymethyloxy-6-methyl-6-(1,4,5
,8-tetramethoxynaphthalen-2-yl)-3,4
,5,6-tetrahydro-2H-pyra 7641■ (95
% yield) as colorless crystals.

m, p, 109-110°C.

[α)"O (cm1.08 chloroform) [) (cr)"-10,3'" (C-1,08rioo
mass spectrum m/e: 569 (M”).

NMR (CDCI,) δ (ppm): 1.84 (
3H, g, 6 CHs), 2.53 (6H.

s, N (CHs)g), 3.02 (IH, t.

J=8.7Hz, Ha), 3.35 (6H, s.

0CHsX2), 3.38 (3H, s.

OCR, ), 3.71.3.84, 3.90°3.92
(121(,4s, Ar0CHsX 4).

3.5-4.2 (2H, m, Hs, Hs).

4.6-5.3 (7H, m, 0CHtOX3゜Hz)
, 6.80 (2H,s,ArH).

7.70 (IH, s, ArH) rR (KBr): l600 (Ar), 10
70°1 040, l O20(-0-) c
m-'.

Elemental analysis value 'C * * Calculated value as Ha s N O□: C, 59,04, H; 7.61°N; 2.4
G%.

Analysis value: C, 58, 86, H; 7.57°N; 2.
40%.

Example 1 (-)-(3S,4R,5R,6R)-4-dimethylamino-2,3,5-)rimethoxymethylsoxy-6-methyl-6-(1,4,5,8- Tetramethoxynaphthalen-2-yl)-3,4゜5.6-tetrahydro-2H
- 300 μm (0.53 mmol) of biran and 8 ml of ethanol
ml of cerium ammonium nitrate at -40°C.
．． A 3 ml aqueous solution of 80 g (3.28 mmol 1) was added and the temperature was raised. After stirring for 10 minutes at 0°C, ethyl acetate 2
0m1. After adding 20 ml of water, and stirring vigorously, saturated sodium bicarbonate solution was added dropwise to adjust the pH of the aqueous layer to -8. After separating the organic layer, it was washed with saturated brine (LOML), and then washed with 0.5N HCl
Back-extract with water (20ml x 2) and add saturated sodium bicarbonate solution to pH-8.
After drying the organic layer with anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure and the resulting residue was purified by silica gel column chromatography (ethyl acetate) to obtain (33,4R ,5R.

6R)-6-(1,4-dimethoxy-5,8-dioxonaphthalen-2-yl)-4-dimethylamino-2,3
,5-trimethoxymethyloxy-6-methyl-3,4
,5,6-tetrahydro-2H-bilane 59w (21%
Yield) was obtained as a yellow caramel.

Mass spectrometry m/e: 539 (M”).

NMR (CDCIs) δ (ppm): 1.81
(3H,s, 6 CHs), 2.48 (6H.

s, N (CHs)t) , 2.83 (L H,t
.

J = 6 Hz, H4), 3.23, 3.39°3.4
0 (9H, 3s, ocHffx 3).

3.82.3.99 (6H, 2s, Ar0CHsX
2), 4.27 (LH, d, J-6Hz.

Hs), 4.5-5.2 (7H, m, OCR, 0x3
．． O-CM-0), 6.76 (2H, s.

8rH), 8.04 (IH, s, ArH).

IR (neat): 1660 (Co).

1040, 1020 (C-0-C) am-basket.

Test example (cancer cell growth inhibition effect) Mouse lymphocytic leukemia cells (p 388) were added to RPme 1640 culture medium containing 10% calf fat serum, and the number of cultured cells was adjusted to 5 x 10 cells/l m 1. and the novel 6-(1,4-dimethoxy-5,8-dioxonaphthalen-2-yl)-3,4,5°6-tetrahydro2 of the present invention.
H- and Ran derivative (1) were added to a predetermined concentration, and the 50% cell growth inhibition concentration [Cso] was determined at 37° C. for 2 days. The results are shown in Table 1.

Table 1 6-(1,4-dimethoxy-5,8-dioxonaphthalen-2-yl)-3,4,5,6-tetrahydro 2
ICs for H(p 38 B).

Claims (1)

[Claims] 6-(1,4-dimethoxy-5,8-dioxonaphthalen-2-yl)-3,4 represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼-(I) , 5,6-tetrahydro-2H-pyran derivative (wherein R^1 is a hydroxyl protecting group).